Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• acids can also impart a reduced tendency for crystallinity in the resulting amino acid derivatives, prohibiting, or at least, severely restricting the use of convenient recrystallization for purification on a multigram-scale. In the case of hydroxy-α-amino acids, any side-chain acylation will, often for

• structure-adapted database searches will uncover such protected amino acid derivatives in abundance, with little effort involved. Part of the reason for the impulsive willingness to adopt protective group chemistry is most surely connected to the fact that only minor quantities of end material are required

• -acetylhydroxyamino acids. They were in fact the first researchers to at all investigate compounds belonging to this class of amino acid derivatives. Under the mantra «acidity favors O-acylation, while alkalinity favors N-acylation», they accomplished this feat by treatment of hydroxy-L-proline, DL-serine, DL

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• N-acyliminium unit [53]. While this reaction proved to be very useful for the cyclization of simple amino acid derivatives, major limitations were encountered when more complicated systems were oxidized [52]. As outlined before, amide groups exhibit rather high oxidation potentials in the order of

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• -based chiral β-amino acid derivatives derived from commercially available (−)-perillaldehyde (1). These 4-isopropyl-substituted analogues of ACHC (2-aminocyclohexanecarboxylic acid) might serve as promising building blocks for the synthesis of chiral 1,3-heterocycles and foldamers [7][11][23][35

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• of imidazole modified pyrimidine and purine derivatives for solid phase synthesis have been described to date [41][44][45][46][47], we believe that the reactions described here serve as an ideal model system, which can be extended to other commercially available amino acid derivatives and nucleosides

• relies on commercially available amino acid derivatives and should be applicable to a large series of natural and unnatural amino acids. Amino acid functionalized nucleosides. Reagents and conditions: a) i. Et3N, Pd(PPh3)4, THF, CO (4 bar), 70 °C, 48 h, ii. Et3N, di-tert-butyl dicarbonate, DMF, rt, 15

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• acid derivatives with imino compounds, or their precursors, is one of the most straightforward synthetic approaches to α,β-diamino acid compounds, in particular in asymmetric mode [14][15][16][17][18][19][20][21][22]. Direct catalytic oxidative diaminations of functionalized alkenes also present an

• corresponding β,γ-amino alcohols and vicinal diamines. α,β-Diamino acid derivatives have been served as organocatalysts, chiral ligands, chiral auxiliaries for asymmertric synthesis [10][11][12], as well as synthetic fragments for peptides and natural products [13]. Mannich-type addition reactions of α-amino

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• 26a and 26c. The final cleavage of the Boc protecting group was carried out in the presence of formic acid at room temperature, affording the target amino acid derivatives 27a and 27c (Scheme 4). Conclusion In conclusion, two complex bridged analogues 27a,c of glutamic acid were synthesized. Starting

• amino acid derivatives 27a and 27c represent useful unnatural amino acid derivatives for both peptidomimetic synthesis and as ligands of the plethora of glutamate receptors. Glutamate receptor ligands. Mechanism for the attack of the carbene intermediate to the olefin moiety 18. Representation of the

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• . However, mass spectrometry has become a major analytical tool in supramolecular chemistry in recent years [19][20][21] and seemed to be perfectly suited in this case, since we were planning to recognise the amino acid derivatives in form of their protonated alkyl esters anyway. Thus, the host–guest

• esters like protonated phenylalanine benzyl ester to make sure that the conditions are mild enough not to cause dissociation. Having made sure that the method is in principle suitable to study the recognition of protonated amino acid derivatives in a competitive fashion there is still one more factor

• that the binding of the amino acid derivatives occurs in a way that puts the substrates in close contact to the crown ether and the spirobifluorene backbone as depicted in motif A in Figure 6 rather than placing them in a more remote position where only the ammonium group can interact with the crown

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• resulted α-amino acid derivatives are useful building blocks in modern organic synthetic and medicinal chemistry [21][22]. For example, we can easily find the active participation of α-imino esters in the total synthesis of the bioactive molecule fumimycin [23]. Moreover, α-amino acids are the most general

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• to expand the available chemical space. The presence of nitrogen in a small 3D structure can be important for its biological activity [14]; this is particularly important when developing unnatural amino acid derivatives [15][16]. Such compounds represent an important contribution to a fragment

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• carbamate protected amino acid derivatives 3 (remaining as impurity in the isolated products 2), quantitative benzylation (1→I) was ensured by successive addition of three portions of benzaldehyde/NaBH4 (Quitt´s procedure [61] → two portions) and by maintaining the pH at a value of 10–11. The extractive

• cis-11a–d and trans-11a (Table 2, Scheme 6 and 7) was determined with HPLC on a chiral stationary phase and comparison with racemic samples (alanine 1a and phenylglycine 1c derived substrates) or in analogy to the aforementioned amino acid derivatives (phenylalanine 1b and methionine 1d deduced

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• (azlactones) are suitable heterocycles to perform this C–C bond generation based strategy affording both quaternized and non quaternized α-amino acid derivatives [2][3][4][5]. The preparation of azlactones is very simple and their reactivity is very diverse due to their functional groups [2][3][4][5]. Many

• order to clarify the enantio- and anomalous regioselectivity. Results and Discussion Initially, the synthesis of oxazolones 5 was accomplished under mild reaction conditions by mixing N-acyl-α-amino acid derivatives in the presence of dehydrating agents such as carbodiimides [2][3][4][5]. Gold(I

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• producing γ-amino acid derivatives with one stereogenic quaternary carbon has been independently developed by Dixon [42] and Jørgensen’s group [43]. Dixon and co-workers discovered that OC-16 bearing bulky substituents both on the 9-O atom and the bridgehead nitrogen afforded excellent enantioselectivity of

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• Marfey’s analysis: Peptide samples (600 μg) were subjected to acid hydrolysis and subsequent Marfey’s analysis in a similar manner as described in [27]. LC–MS analysis (ESIMS, positive ion mode): individual FDAA-amino acid peak was identified by co-injection with standard amino acid derivatives. The

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• spirocyclic carbocyclic systems [3], cyclic amino acid derivatives [4], cyclic ethers [5][6], and lactones [7][8]. In most of these examples, the reactions can be viewed as arising from an oxidation that forms an olefinic radical cation that is then rapidly trapped by a nucleophile. This triggers a cascade of

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• skeleton is frequently used as a pharmacophore for the modification of known pharmaceuticals. Triazole analogues of several bioactive compounds have recently been reported. Examples are those of the well-known highly functionalized antiviral cyclic amino acid derivatives oseltamivir and zanamivir (5 and 6

• synthetic 4-methylene derivative icofungipen (8), also an antifungal agent, is now proceeding through clinical development for the oral treatment of yeast infections (Figure 2) [24]. Certain multi-substituted cyclohexane amino acid derivatives, such as oryzoxymycin (9) and tilidine (10), are also well-known

• dipolarophiles to yield a library of novel 1,2,3-triazole-modified cyclic β-amino acid derivatives. Compounds 11–14 were racemates, the structures in Table 1 show their relative stereochemistry. The CF syntheses were carried out under both conditions A and B in order to obtain a clear comparison between the

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• 9 in good yield (Scheme 2). The synthetic route presented above could be extended to the preparation of other 4-fluorinated cyclohexane amino acid derivatives, stereoisomers of 7 or 9. Ethyl trans-2-aminocyclohex-4-enecarboxylate 10 [57] was analogously transformed to its cis counterpart through

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• myriad of enantioselective transformations, e.g., with aromatic or aliphatic enones [1]. There are many approaches employing protonated derivatives of chinchona alkaloids [2][3][4][5], amino acid derivatives, and chiral 1,2-diamines, which provide excellent yields and enantioselectivities. Among the most

• direct aldol reaction, which is mediated by copper ions and amino acid derivatives [14] or enamine nucleophilic addition to palladium π-allyl electrophiles [15][16][17]. We report the development of new catalysts based on chiral 1,2-diamines and present their application in the asymmetric addition of 4

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• . Alkylation of imine Alkylation of glycine imine by using a chiral phase-transfer catalyst emerged as a very good strategy for the asymmetric synthesis of amino-acid derivatives [59][60][61]. Lamaty and co-workers prepared a series of glycine Schiff bases 22 in excellent yield (97–98%) in short reaction time

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• -functionality, which is often difficult and low yielding [11][12][13][14][15]. Ring opening of N-unfunctionalised (NH-) aziridines allows direct access to amino-acid derivatives, yet the published methodology is currently limited for this transformation [16][17][18][19][20]. In literature examples where ring

• ring opening of aziridine 1a, derived from tert-butyl cinnamate. As a result, a diverse array of amino-acid derivatives is generated in three steps from commercially available starting materials. Results and Discussion The aziridination of tert-butyl cinnamate was the starting point chosen for our

• -aziridines to ring-opening chemistry. To the best of our knowledge, only four papers exist detailing the regioselective ring opening of NH-aziridine-2-carboxylates to provide amino-acid derivatives [16][17][18][19]. The substrate scope has been limited to NH-aziridine-2-carboxylates derived from isopropyl

Binaphthyl-anchored antibacterial tripeptide derivatives with hydrophobic C-terminal amino acid variations

• John B. Bremner,
• Paul A. Keller,
• Stephen G. Pyne,
• Mark J. Robertson,
• K. Sakthivel,
• Kittiya Somphol,
• Dean Baylis,
• Jonathan A. Coates,
• John Deadman,
• Dharshini Jeevarajah and
• David I. Rhodes

Beilstein J. Org. Chem. 2012, 8, 1265–1270, doi:10.3762/bjoc.8.142

• 2b. The results of these synthetic and antibacterial testing studies are reported in this paper. Results and Discussion A concise and flexible approach to all the target compounds 2a–g was used, starting from the commercially available amino acid derivatives 3 and proceeding via the amino benzyl

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• sequence was synthesized on a preloaded 2-chlorotrityl chloride resin (Carbolution Chemicals, Germany) on a 50 μmol scale with the Discover CEM System by using standard 9-fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) chemistry. An amount of 6 equiv of amino-acid derivatives (>98%; Iris Biotech, Germany

Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines

• Melinda Nonn,
• Loránd Kiss,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10

• cispentacin stereoisomer 2 into multifunctionalized β-amino acid derivative 12. Synthesis of multifunctionalized β-amino acid derivatives 13–16. Reaction conditions: NaBH4, NiCl2, Boc2O, EtOH/H2O, rt, 6 h. Acknowledgements We are grateful to the Hungarian Research Foundation (OTKA No. T81371) for financial

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution

• Xiao-bo Zhou,
• Wing-Hong Chan,
• Albert W. M. Lee and
• Chi-Chung Yeung

Beilstein J. Org. Chem. 2011, 7, 1508–1515, doi:10.3762/bjoc.7.176

• enantioselectivity on Cys for the first time. Experimental Proton NMR spectra were recorded on a Bruker Avance-III 400 spectrometer at 400 MHz in DMSO-d6. Fluorescence emission spectra and UV–vis spectra were collected on a PE LS50B and a Cary UV-100 spectrometer, respectively. All inorganic reagents and amino acid

• derivatives were of analytical reagent grade and were obtained from Aldrich or Sigma. ACAQ was synthesized according to our method [16]. The stock solution of 1.0 × 10−3 M ACAQ was obtained by dissolution of the compound in ACN. The stock solutions of 5.0 × 10−3 M amino acids were prepared by dissolution of

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• conclusion, we showed that the ring opening of epoxides, either directly or Pd-catalyzed, with chelated enolates combined with Passerini reactions is a suitable tool for the synthesis of highly functionalized α-hydroxy and α-amino acid derivatives. These new compounds are interesting building blocks for